TY - JOUR
T1 - A neuroprotective herbal mixture inhibits caspase-3-independent apoptosis in retinal ganglion cells
AU - Cheung, Zelda H.
AU - Leung, Mason C.P.
AU - Yip, Henry K.
AU - Wu, Wutian
AU - Siu, Flora K.W.
AU - So, Kwok Fai
N1 - Funding Information:
Acknowledgements The authors would like to thank Miss Reiko Cheung and Mr. K.K. Yip for their technical assistance in the Western blotting. This research is supported by donations from the Hong Kong Charitable Foundation, and Ms. Annie Tsao Wen Wei, and an ASD grant from the Hong Kong Polytechnic University, China. Z.H. Cheung was supported by a scholarship from the Croucher Foundation, Hong Kong.
PY - 2008/1
Y1 - 2008/1
N2 - It was previously demonstrated that Menta-FX, a mixture of Panax quinquefolius L. (PQE), Ginkgo biloba (GBE), and Hypericum perforatum extracts (HPE), enhances retinal ganglion cell survival after axotomy. However, the mechanisms of neuroprotection remain unknown. The aim of this study is to elucidate the neuroprotective mechanisms of Menta-FX. Since PQE, GBE and HPE have all been observed to display anti-oxidative property, the involvement of anti-oxidation in Menta-FX's neuroprotective effect was investigated. Menta-FX lowered nitric oxide (NO) content in axotomized retinas without affecting nitric oxide synthase activity, suggesting that Menta-FX possibly exhibited a NO scavenging property. In addition, the effect of Menta-FX on the frequency of axotomy-induced nuclear fragmentation and caspase-3 activation was investigated. Menta-FX treatment significantly reduced nuclear fragmentation in axotomized retinas. Surprisingly, Menta-FX had no effect on caspase-3 activation, but selectively lowered caspase-3-independent nuclear fragmentation in axotomized retinal ganglion cells. In addition, inhibition of PI3K activity by intravitreal injection of wortmannin, a phosphoinositide-3 kinase (PI3K) inhibitor, completely abolished the neuroprotective effect of Menta-FX, indicating that Menta-FX's neuroprotective effect was PI3K-dependent. Data here suggest that Menta-FX displayed a PI3K-dependent, selective inhibition on a caspase-3-independent apoptotic pathway in axotomized RGCs, thus, highlighting the potential use of herbal remedies as neuroprotective agents for other neurodegenerative diseases.
AB - It was previously demonstrated that Menta-FX, a mixture of Panax quinquefolius L. (PQE), Ginkgo biloba (GBE), and Hypericum perforatum extracts (HPE), enhances retinal ganglion cell survival after axotomy. However, the mechanisms of neuroprotection remain unknown. The aim of this study is to elucidate the neuroprotective mechanisms of Menta-FX. Since PQE, GBE and HPE have all been observed to display anti-oxidative property, the involvement of anti-oxidation in Menta-FX's neuroprotective effect was investigated. Menta-FX lowered nitric oxide (NO) content in axotomized retinas without affecting nitric oxide synthase activity, suggesting that Menta-FX possibly exhibited a NO scavenging property. In addition, the effect of Menta-FX on the frequency of axotomy-induced nuclear fragmentation and caspase-3 activation was investigated. Menta-FX treatment significantly reduced nuclear fragmentation in axotomized retinas. Surprisingly, Menta-FX had no effect on caspase-3 activation, but selectively lowered caspase-3-independent nuclear fragmentation in axotomized retinal ganglion cells. In addition, inhibition of PI3K activity by intravitreal injection of wortmannin, a phosphoinositide-3 kinase (PI3K) inhibitor, completely abolished the neuroprotective effect of Menta-FX, indicating that Menta-FX's neuroprotective effect was PI3K-dependent. Data here suggest that Menta-FX displayed a PI3K-dependent, selective inhibition on a caspase-3-independent apoptotic pathway in axotomized RGCs, thus, highlighting the potential use of herbal remedies as neuroprotective agents for other neurodegenerative diseases.
KW - Ganglion cells
KW - Ginkgo biloba
KW - Hypericum perforatum
KW - Optic nerve
KW - Panax quinquefolius L.
UR - http://www.scopus.com/inward/record.url?scp=39149102105&partnerID=8YFLogxK
U2 - 10.1007/s10571-007-9175-8
DO - 10.1007/s10571-007-9175-8
M3 - Article
C2 - 17710535
AN - SCOPUS:39149102105
SN - 0272-4340
VL - 28
SP - 137
EP - 155
JO - Cellular and Molecular Neurobiology
JF - Cellular and Molecular Neurobiology
IS - 1
ER -